Evidence map›Paper›PMID 12646859›Full record

ArticleGene therapy2003

Hypoxia-mediated tumour targeting.

K Binley, Z Askham, L Martin, H Spearman, D Day, S Kingsman, S Naylor

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 94 citations in OpenAlex.

  1. Article
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  4. Endothelial cell calpain as a critical modulator of angiogenesis.Biochimica et biophysica acta. Molecular basis of disease · 2017
    Review
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  11. Hypoxia targeted bifunctional suicide gene expression enhances radiotherapy in vitro and in vivo.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2012
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

K BinleyOxford BioMedica (UK) Ltd, Medawar Centre, Oxford Science Park, Oxford, UK.
Z Askham
L Martin
H Spearman
D Day
S Kingsman
S Naylor
Oxford BioMedica (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia is a common physiological feature of tumours. It activates a signalling cascade that culminates in the stabilization of the HIF-1 transcription factor and activation of genes that possess a hypoxia response element (HRE). We have used an optimized hypoxia responsive promoter (OBHRE) to investigate hypoxia-targeted gene expression in vivo in the context of an adenovirus vector. The OBHRE promoter showed limited activity in the liver or spleen such that expression was 1000-fold lower than that driven by the strong CMV/IE promoter. However, in the context of the tumour microenvironment, the OBHRE promoter achieved expression levels comparable to that of the CMV/IE promoter. Next, we showed that an adenovirus expressing the human cytochrome P450 (CYP2B6) regulated by the OBHRE promoter delays tumour growth in response to the prodrug cyclophosphamide (CPA). Finally, we exploited the hepatotropism of adenovirus to investigate whether the OBHRE promoter could mitigate the hepatotoxicity of a recombinant adenovirus expressing thymidine kinase (TK) in the context of the prodrug ganciclovir (GCV). High-dose Ad.CMVTK/GCV treatment caused significant liver necrosis whereas the same dose of Ad.HRETK was well tolerated. These in vivo data demonstrate that hypoxia-targeted gene expression via the OBHRE promoter can be used to increase the therapeutic window of cytotoxic cancer gene therapy.

Indexed as

Promoter Regions, GeneticAdenoviridaeAnimalsAntiviral AgentsBreast NeoplasmsCyclophosphamideCytomegalovirusFemaleGanciclovirGene ExpressionGene TargetingGenetic EngineeringGenetic TherapyGenetic VectorsHypoxiaHypoxia, BrainAntiviral AgentsCyclophosphamideGanciclovirProdrugsThymidine Kinase

Identifiers

PMID12646859
OpenAlexW2091781047

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.